CancerREFLEXNCT07405385
REstoring Metabolic FLEXibility Through Combined Exercise in Breast Cancer Survivors: A Randomized Controlled Trial.
A study testing Exercise in people with Cancer and Breast Cancer, run by University of Castilla-La Mancha at 1 site in Spain.
Trial summary
The REFLEX study is a randomized, controlled clinical trial designed to evaluate the impact of a 16-week supervised, combined exercise program on metabolic flexibility and cardiorespiratory fitness in breast cancer survivors. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Cancer, Breast Cancer, Neoplasm
- What is being tested?
- Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteSpain
- Study dates
- Sep 2026to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women aged between 18 and 70 years.
- Confirmed diagnosis of breast cancer in stages I to III.
- Received neo-adjuvant or adjuvant chemotherapy and completed the chemotherapy treatment within the 6 months prior to study enrolment.
- Residency within a distance of less than 40 km from the Hospital Universitario de Toledo.
Who cannot join
- Diagnosis of stage IV breast cancer.
- Undergone major surgery within the 4 months prior to enrolment or scheduled for breast reconstruction surgery during the study period.
- Diagnosis of diabetes mellitus with poor glycaemic control, defined as an HbA1c value greater than or equal to 8.5%.
- Presence of an acute infectious disease.
- Absolute or relative medical contraindications for physical exercise or maximal exercise stress testing, according to the American College of Sports Medicine (ACSM) guidelines.
- Serious cardiac or cardiovascular disease, including a history of myocardial infarction, heart failure, or known cardiomyopathy.
- Regular consumption of beta-blockers or any medication that alters the functioning of the nervous system.
- Currently active, defined as engaging in more than 150 minutes per week of structured physical exercise during the 6 months prior to enrolment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
University of Castilla-La Mancha (PAFS Research Group)
Toledo, Toledo, 45071
Susana Aznar Laín, +34 669356600, susana.aznar@uclm.es
About this study
The REFLEX study is a randomized, controlled clinical trial designed to evaluate the impact of a 16-week supervised, combined exercise program on metabolic flexibility and cardiorespiratory fitness in breast cancer survivors. While cancer treatments have significantly improved survival rates, the disease and its therapies often cause systemic mitochondrial dysfunction and muscle loss. This leads to persistent "metabolic inflexibility"-a reduced ability to efficiently switch between burning carbohydrates and fats for energy. This inflexibility, exacerbated by sedentary behavior and cancer-related fatigue, can severely diminish a patient's functional autonomy and overall quality of life. The trial focuses on assessing whether exercise can restore this metabolic adaptability in women aged 18 to 70 with stage I-III breast cancer who are currently on hormonal treatment and completed neo/adjuvant chemotherapy within the past 6 months.
The study operates on the primary hypothesis that an individualized exercise intervention will significantly improve the participants' metabolic flexibility-measured via the metabolic crossover point-and overall aerobic capacity (VO2max) when compared to a control group. Additionally, the trial will analyze secondary outcomes, including changes in cardiovascular and metabolic risk factors, muscle strength, body composition (such as bone mineral density), and patient-reported outcomes assessing quality of life, fatigue, joint pain, anxiety, and depression.
Read more
A total of 44 participants will be randomly assigned to either the intervention or control group. Participants in the intervention group will complete a 16-week program consisting of two weekly supervised sessions. Each session lasts between 55 and 85 minutes and includes a tailored combination of aerobic and strength training based on the individual's baseline fitness and metabolic thresholds. Participants in the control group. will receive standard educational materials via email, featuring healthy lifestyle and exercise guidelines from the World Health Organization (WHO) and the American College of Sports Medicine (ACSM).
To evaluate the program's effectiveness, comprehensive medical and functional assessments will be conducted at baseline, immediately after the 16-week intervention, and at a 3-month follow-up. These evaluations include submaximal and maximal exercise tests on a cycle ergometer to analyze respiratory gases, detailed blood tests, body composition imaging (DXA scans), and maximum dynamic strength testing. Ultimately, the research aims to generate high-quality evidence to optimize standard exercise recommendations for breast cancer survivors and improve their long-term health and resilience.
- Conditions
- Cancer, Breast Cancer, Neoplasm, Metabolic Flexibility
- Being tested
- Control, Exercise
- Medical subject headings
- Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ControlBehavioural
Participants assigned to the control group receive standard care typically provided to patients in this phase of recovery. Instead of a supervised exercise program, these individuals are sent educational materials via email. This material consists of a video and official documents containing basic guidelines and recommendations for a healthy lifestyle, based on standards from the World Health Organization (WHO) and the American College of Sports Medicine (ACSM) for cancer survivors. The documents provide general instructions on physical activity, reducing sedentary behavior, and maintaining overall health habits. Like the intervention group, participants in the control group undergo all clinical and functional evaluations at the start of the study, after 16 weeks, and during a 3-month follow-up.
ExerciseBehavioural
The intervention consists of a supervised, in-person, combined exercise program lasting 16 consecutive weeks, conducted at a specialized exercise unit. Participants attend two sessions per week, with at least 48 hours of recovery between sessions, and each session lasts between 55 and 85 minutes. The program follows a "combined" methodology, meaning every session integrates both resistance (strength) and aerobic training. To ensure safety and precision, sessions are led by a graduate in Physical Activity and Sport Sciences with specialized training in oncology, and participants work in small groups of 6 to 8 people.
Each session is structured into four distinct parts: a 10-minute warm-up involving low-to-moderate intensity activity and joint mobility; a resistance training block; an aerobic training block; and a cool-down featuring static stretching for 30-40 seconds per muscle group. The resistance training portion utilizes a "full body" approach.
| Study group | Role | What they receive |
|---|---|---|
| EXERCISE GROUP | Experimental | Not described Receives: Behavioral: Exercise |
| CONTROL GROUP | Other | Not described Receives: Behavioral: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Crossover point
Assessment of the metabolic crossover point determined through an individualized, submaximal incremental exercise test on a cycle ergometer with continuous measurement of expired gases (indirect calorimetry) to calculate substrate oxidation rates.
Measured: 7 months
Changes in Cardiorespiratory Fitness
Assessment of cardiorespiratory capacity determined through a maximal cardiopulmonary exercise test (stress test) on a cycle ergometer
Measured: 7 months
Secondary outcomes (15)
Change in maximal fat oxidation
Assessment of the maximal fat oxidation rate determined through an individualized, submaximal incremental exercise test on a cycle ergometer with continuous measurement of expired gases (indirect calorimetry).
Measured: 7 months
Change in maximal carbohydrate oxidation
Assessment of the maximal carbohydrate oxidation rate determined through an individualized, submaximal incremental exercise test on a cycle ergometer with continuous measurement of expired gases (indirect calorimetry).
Measured: 7 months
Change in Lower Body Muscular Strength
Estimated one-repetition maximum (1RM) for the leg press. Measurements will be obtained through force-velocity profiling using a linear position transducer.
Measured: 7 months
Change in Upper-Body Muscular Strength
Estimated one-repetition maximum (1RM) for the vertical press. Measurements will be obtained through force-velocity profiling using a linear position transducer.
Measured: 7 months
Change in 6-Minute Walk Test
Evaluation of physical performance using the 6-minute walk test.
Measured: 7 months
Change in Lower-Body Muscular Endurance (30-sec CST)
Evaluation of physical performance using the 30-second chair stand test.
Measured: 7 months
Change in Grip Strength
Evaluation of upper-body isometric strength using a handheld dynamometer.
Measured: 7 months
Change in Body Mass Index (BMI)
BMI will be calculated as weight in kilograms divided by height in meters squared (kg/m2).
Measured: 7 months
Change in Body Fat Percentage
Assessment of total body fat percentage using Dual-Energy X-ray Absorptiometry (DXA) scan.
Measured: 7 months
Change in Lean Mass Percentage
Assessment of total lean muscle mass percentage using Dual-Energy X-ray Absorptiometry (DXA) scan.
Measured: 7 months
Change in Bone Mineral Density
Assessment of bone mineral density (g/cm²) determined through a Dual-Energy X-ray Absorptiometry (DXA) scan.
Measured: 7 months
Change in EQ-5D-5L Visual Analogue Scale (VAS)
Evaluation of self-rated health using the EuroQol Visual Analogue Scale (EQ VAS). The scale is a vertical line with minimum value 0 (worst imaginable health) and maximum value 100 (best imaginable health). Higher scores indicate a better perceived health outcome.
Measured: 7 months
Change in EQ-5D-5L Index Score
Evaluation of health-related quality of life based on the EuroQol 5-dimension 5-level (EQ-5D-5L) descriptive system. This system assesses five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses are converted into a single index score using a valuation algorithm. The index scale typically ranges from less than 0 to 1, where higher scores indicate a better outcome.
Measured: 7 months
Change from Baseline in Cancer-Related Fatigue (FACIT-F)
Evaluation using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Total scores range from 0 to 52, where higher scores indicate lower levels of fatigue.
Measured: 7 months
Change in Hospital Anxiety and Depression Scale (HADS)
Evaluation using the Hospital Anxiety and Depression Scale (HADS). The total score ranges from 0 to 42, where higher scores indicate greater psychological distress.
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2026
- Study startSep 2026 (estimated)
- Primary completionAug 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Castilla-La Mancha
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Susana Aznar Laín, University of Castilla-La Mancha
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07405385
- Sponsor's protocol ID
- 2024-UNIVERS-12844
- Acronym
- REFLEX
- Status last verified
- Jan 2026
- First submitted
- 27 Jan 2026
- Last updated
- 28 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REstoring Metabolic FLEXibility Through Combined Exercise in Breast Cancer Survivors: A Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT07405385
- Acronym / sponsor ID
- REFLEX / 2024-UNIVERS-12844
- Conditions
- Cancer, Breast Cancer, Neoplasm, Metabolic Flexibility
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- University of Castilla-La ManchaUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 12 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The REFLEX study is a randomized, controlled clinical trial designed to evaluate the impact of a 16-week supervised, combined exercise program on metabolic flexibility and cardiorespiratory fitness in breast cancer survivors. While cancer treatments have significantly improved survival rates, the disease and its therapies often cause systemic mitochondrial dysfunction and muscle loss. This leads to persistent "metabolic inflexibility"-a reduced ability to efficiently switch between burning carbohydrates and fats for energy. This inflexibility, exacerbated by sedentary behavior and cancer-related fatigue, can severely diminish a patient's functional autonomy and overall quality of life. The trial focuses on assessing whether exercise can restore this metabolic adaptability in women aged 18 to 70 with stage I-III breast cancer who are currently on hormonal treatment and completed neo/adjuvant chemotherapy within the past 6 months.
The study operates on the primary hypothesis that an individualized exercise intervention will significantly improve the participants' metabolic flexibility-measured via the metabolic crossover point-and overall aerobic capacity (VO2max) when compared to a control group. Additionally, the trial will analyze secondary outcomes, including changes in cardiovascular and metabolic risk factors, muscle strength, body composition (such as bone mineral density), and patient-reported outcomes assessing quality of life, fatigue, joint pain, anxiety, and depression.
A total of 44 participants will be randomly assigned to either the intervention or control group. Participants in the intervention group will complete a 16-week program consisting of two weekly supervised sessions. Each session lasts between 55 and 85 minutes and includes a tailored combination of aerobic and strength training based on the individual's baseline fitness and metabolic thresholds. Participants in the control group. will receive standard educational materials via email, featuring healthy lifestyle and exercise guidelines from the World Health Organization (WHO) and the American College of Sports Medicine (ACSM).
To evaluate the program's effectiveness, comprehensive medical and functional assessments will be conducted at baseline, immediately after the 16-week intervention, and at a 3-month follow-up. These evaluations include submaximal and maximal exercise tests on a cycle ergometer to analyze respiratory gases, detailed blood tests, body composition imaging (DXA scans), and maximum dynamic strength testing. Ultimately, the research aims to generate high-quality evidence to optimize standard exercise recommendations for breast cancer survivors and improve their long-term health and resilience.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EXERCISE GROUP | Experimental | Behavioral: Exercise |
| CONTROL GROUP | Other | Behavioral: Control |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Women aged between 18 and 70 years.
- Confirmed diagnosis of breast cancer in stages I to III.
- Received neo-adjuvant or adjuvant chemotherapy and completed the chemotherapy treatment within the 6 months prior to study enrolment.
- Residency within a distance of less than 40 km from the Hospital Universitario de Toledo.
Key exclusion criteria (8 listed)
- Diagnosis of stage IV breast cancer.
- Undergone major surgery within the 4 months prior to enrolment or scheduled for breast reconstruction surgery during the study period.
- Diagnosis of diabetes mellitus with poor glycaemic control, defined as an HbA1c value greater than or equal to 8.5%.
- Presence of an acute infectious disease.
- Absolute or relative medical contraindications for physical exercise or maximal exercise stress testing, according to the American College of Sports Medicine (ACSM) guidelines.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ControlParticipants assigned to the control group receive standard care typically provided to patients in this phase of recovery. Instead of a supervised exercise program, these individuals are sent educational materials via email. This material consists of a video and official documents containing basic guidelines and recommendations for a healthy lifestyle, based on standards from the World Health Organization (WHO) and the American College of Sports Medicine (ACSM) for cancer survivors. The documents provide general instructions on physical activity, reducing sedentary behavior, and maintaining overall health habits. Like the intervention group, participants in the control group undergo all clinical and functional evaluations at the start of the study, after 16 weeks, and during a 3-month follow-up. | Behavioural | CONTROL GROUP |
| ExerciseThe intervention consists of a supervised, in-person, combined exercise program lasting 16 consecutive weeks, conducted at a specialized exercise unit. Participants attend two sessions per week, with at least 48 hours of recovery between sessions, and each session lasts between 55 and 85 minutes. The program follows a "combined" methodology, meaning every session integrates both resistance (strength) and aerobic training. To ensure safety and precision, sessions are led by a graduate in Physical Activity and Sport Sciences with specialized training in oncology, and participants work in small groups of 6 to 8 people. Each session is structured into four distinct parts: a 10-minute warm-up involving low-to-moderate intensity activity and joint mobility; a resistance training block; an aerobic training block; and a cool-down featuring static stretching for 30-40 seconds per muscle group. The resistance training portion utilizes a "full body" approach. | Behavioural | EXERCISE GROUP |
Primary outcome
Change in Crossover point
Time frame: 7 months
Assessment of the metabolic crossover point determined through an individualized, submaximal incremental exercise test on a cycle ergometer with continuous measurement of expired gases (indirect calorimetry) to calculate substrate oxidation rates.
Changes in Cardiorespiratory Fitness
Time frame: 7 months
Assessment of cardiorespiratory capacity determined through a maximal cardiopulmonary exercise test (stress test) on a cycle ergometer
15 secondary outcomes
Change in maximal fat oxidation
Time frame: 7 months
Change in maximal carbohydrate oxidation
Time frame: 7 months
Change in Lower Body Muscular Strength
Time frame: 7 months
Change in Upper-Body Muscular Strength
Time frame: 7 months
Change in 6-Minute Walk Test
Time frame: 7 months
Change in Lower-Body Muscular Endurance (30-sec CST)
Time frame: 7 months
Change in Grip Strength
Time frame: 7 months
Change in Body Mass Index (BMI)
Time frame: 7 months
Change in Body Fat Percentage
Time frame: 7 months
Change in Lean Mass Percentage
Time frame: 7 months
Change in Bone Mineral Density
Time frame: 7 months
Change in EQ-5D-5L Visual Analogue Scale (VAS)
Time frame: 7 months
Change in EQ-5D-5L Index Score
Time frame: 7 months
Change from Baseline in Cancer-Related Fatigue (FACIT-F)
Time frame: 7 months
Change in Hospital Anxiety and Depression Scale (HADS)
Time frame: 7 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise in people with Cancer and Breast Cancer, run by University of Castilla-La Mancha at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Susana Aznar Laín (+34 669356600, susana.aznar@uclm.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Crossover point (time frame: 7 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.